Hormonal
Low-dose lithium supplementation (1-25 mM in Drosophila) extends median and maximum lifespan and healthspan independently of sex and genetic background.
This study identifies lithium as a pro-longevity agent in fruit flies, extending lifespan by 16-18% at low doses (1-25 mM) without reducing food intake or fertility. The mechanism involves inhibiting GSK-3 to activate NRF-2, enhancing stress resistance. While promising, human translation requires caution due to the narrow therapeutic window and potential toxicity at higher doses. Future human trials may explore low-dose, intermittent, or late-life administration to maximize benefits while minimizing renal risks.
Lithium treatment in the range of 1 to 25 mM resulted in lifespan extension... These effects of lithium treatment on lifespan extension were also observed in an independent genetic background... and in males... Thus, lithium treatment extended Drosophila lifespan independently of genetic background and sex.
Why this rating
High-quality experimental data in a model organism (Drosophila) with clear dose-response relationships and genetic validation.
Source
Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis
Jorge Iván Castillo-Quan et al. · Cell Reports · 2016
DOI 10.1016/j.celrep.2016.03.041
More from this paper
- Lithium extends lifespan and stress resistance by inhibiting GSK-3 (Shaggy in flies), which subsequently activates the transcription factor NRF-2 (CncC), leading to hormetic stress resistance.Strong
- There is a hormetic curve for NRF-2 activation: low-level activation extends lifespan, while high-level activation (e.g., via Keap1 deletion combined with lithium) shortens lifespan or provides no additional longevity benefit, though it increases stress resistance.Good
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